chr15-67589591-G-C

Variant names:

• chr15-67589591-G-C
• rs6494673
• NM_145160.3:c.431+2678G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_145160.3(MAP2K5):​c.431+2678G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,088 control chromosomes in the GnomAD database, including 2,069 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2069 hom., cov: 32)
• Consequence: MAP2K5 NM_145160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 3 publications found

Genes affected

MAP2K5 (HGNC:6845): (mitogen-activated protein kinase kinase 5) The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been described. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	NM_145160.3	MANE Select	c.431+2678G>C		intron	N/A	NP_660143.1
	MAP2K5	NM_002757.4		c.431+2678G>C		intron	N/A	NP_002748.1
	MAP2K5	NM_001206804.2		c.323+2678G>C		intron	N/A	NP_001193733.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K5	ENST00000178640.10	TSL:1 MANE Select	c.431+2678G>C		intron	N/A	ENSP00000178640.5
	MAP2K5	ENST00000395476.6	TSL:1	c.431+2678G>C		intron	N/A	ENSP00000378859.2
	MAP2K5	ENST00000354498.9	TSL:2	c.323+2678G>C		intron	N/A	ENSP00000346493.5

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22111 AN: 151968 Hom.: 2064 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22135 AN: 152088 Hom.: 2069 Cov.: 32 AF XY: 0.149 AC XY: 11088 AN XY: 74354

African (AFR) AF: 0.254 AC: 10550 AN: 41464

American (AMR) AF: 0.122 AC: 1862 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 228 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1049 AN: 5172

South Asian (SAS) AF: 0.104 AC: 504 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1613 AN: 10546

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5972 AN: 68010

Other (OTH) AF: 0.129 AC: 273 AN: 2110

Alfa AF: 0.0567 Hom.: 57

Bravo AF: 0.148

Asia WGS AF: 0.125 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6494673; hg19: chr15-67881929;